rs2483853

Variant names:

• chr10-127142042-A-G
• rs2483853
• NM_001290223.2:c.2847+14278A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001290223.2(DOCK1):​c.2847+14278A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 152,132 control chromosomes in the GnomAD database, including 18,618 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.47 (18618 hom., cov: 33)
• Consequence: DOCK1 NM_001290223.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256
• Publications: 3 publications found

Genes affected

DOCK1 (HGNC:2987): (dedicator of cytokinesis 1) This gene encodes a member of the dedicator of cytokinesis protein family. Dedicator of cytokinesis proteins act as guanine nucleotide exchange factors for small Rho family G proteins. The encoded protein regulates the small GTPase Rac, thereby influencing several biological processes, including phagocytosis and cell migration. Overexpression of this gene has also been associated with certain cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

INSYN2A (HGNC:33859): (inhibitory synaptic factor 2A) Predicted to be involved in inhibitory postsynaptic potential. Predicted to be active in postsynaptic density. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.2847+14278A>G		intron_variant	Intron 27 of 51	ENST00000623213.2	NP_001277152.2
INSYN2A	NM_001039762.3	c.1257-4022T>C		intron_variant	Intron 5 of 5	ENST00000522781.6	NP_001034851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK1	ENST00000623213.2	c.2847+14278A>G		intron_variant	Intron 27 of 51	1	NM_001290223.2	ENSP00000485033.1
INSYN2A	ENST00000522781.6	c.1257-4022T>C		intron_variant	Intron 5 of 5	2	NM_001039762.3	ENSP00000429763.1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70765 AN: 152014 Hom.: 18619 Cov.: 33

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.739

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.469

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.465 AC: 70767 AN: 152132 Hom.: 18618 Cov.: 33 AF XY: 0.463 AC XY: 34444 AN XY: 74384

African (AFR) AF: 0.204 AC: 8459 AN: 41514

American (AMR) AF: 0.525 AC: 8015 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1997 AN: 3472

East Asian (EAS) AF: 0.584 AC: 3013 AN: 5162

South Asian (SAS) AF: 0.478 AC: 2304 AN: 4822

European-Finnish (FIN) AF: 0.500 AC: 5292 AN: 10592

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.586 AC: 39839 AN: 67982

Other (OTH) AF: 0.466 AC: 984 AN: 2110

Alfa AF: 0.552 Hom.: 39782

Bravo AF: 0.458

Asia WGS AF: 0.492 AC: 1715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.97
DANN	Benign	0.70
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2483853; hg19: chr10-128940306;